We propose to continue our multidisciplinary research program which will integrate substantial institutional expertise in infectious diseases, neurology, immunology, retrovirology and herpes viruses, parasitology, agents active against these agents, and numerous clinical resources in both South Carolina and North Carolina focusing on the evaluation of novel therapies for HIV-infected persons. A group of clinical investigators at UNC as well as 4 satellite units in Charlotte, Greensboro, Raleigh and Charleston, South Carolina will collectively study new compounds active against HIV and associated diseases in 150 new patients and 277 previously enrolled patients in a timely and cost-effective manner. We shall continue our high rate of accrual among minorities, women and IVDUs. Trials will be of all phases (I, II, III) and types (primary infection, opportunistic infection, neurology, malignancy). Patients will be followed for in vivo evidence of study drug effects on HIV, EBV, CMV, HSV and other opportunistic infections using our core virology laboratory. Pharmacokinetics will be monitored in our General Clinical Research Center. Concepts for new protocols will originate with the investigators, through participation in ACTG committees and the newly established scientific advisory board. Outreach to the community and local physicians will be accomplished through our community advisory boards at each site, our statewide newsletter, and continuing education lectures around the state. Links will continue with 5 other major NIH-funded clinical research grants and 4 different NIH training grants.